Acute myocardial infarction is characterized by.heterogeneous tissue injury affecting many aspects of myocardial function. Positron emission tomography (PET) in combination with tracers labeled with short-lived radionuclides allows the in-vivo assessment of specific physiologic and biochemical processes. Such physiologic imaging provide unique tissue characterization in patients with acute myocardial infarction. The extent of ischemic injury can be more accurately assessed than possible with any other non-invasive technique currently available. This proposal will focus on the on the quantitative determination of regional my cardial blood flow, the metabolic differentiation of reversible and irreversible tissue injury and the evaluation of regional catecholamine uptake by adrenergic nerve terminals in patients vith acute myocardial infarction. A new PET approach employing the flow tracer N-13 aumnia in combination with a 3-compartmental tracer kinetic model wi be validated in normal and reperfused canine myocardium using microopheres blood fl. measurements as a gold standard. Metabolic imaging with F-18 deoxyglucose and C-11 ac tate will be used to quantitatively assess oxidative and non-oxidative substrate met bolism by dynamic PET imaging and tracer kineti principles. Animal studies will a dress the value of C-11 acetate kinetics as marker of TCA cycle flux to define tiss viability. Clinically, the metabolic recovery of reperfused human myocardium will characterized and th diagnostic accuracy of the combined evaluation of flow reser and glucose utilization for definition of myor-ardium at risk and extent of necros determined. Finally, the new catecholamine analog C-11 hydroxyephedrine, which traces specifically norepinephrine uptake and storage in adrenergic nerve terminals, will used to relate regional, neuronal function to regiona blood flow and metabolism experimental and clinical myocardial infarction. Correlation of regional neuronal function with the results of electrophysiologic studies will define the potential roll of "neuronal imaging" to identify high risk patients for fatal arrhythmias. The proposed research will provide new insights into substrate metabolism and neuronal function, which is expected to result in new imaging approache for the early assessment of tissue damage, risk stratification and optimization of therapeutic strategies in patients with acute infarction.